Progress in engineered bacterial cancer therapies

Engineered bacteria are emerging as powerful tools in the development of cancer therapies, driven by advances in synthetic biology and tumor immunology. These microbes preferentially colonize solid tumors, where they can deliver therapeutic agents directly to malignant cells and into the tumor microenvironment, inducing tumor cell death and activating robust anti-tumor immune responses. Current strategies include programming bacteria to secrete toxins, tumor-suppressor or pro-apoptotic proteins, and to mediate targeted intracellular delivery. Bacteria can also be engineered to sense tumor-specific metabolites and to adhere to tumor-associated cell surface antigens, further enhancing selectivity and safety. Engineered strains synergize with immunotherapies - including immune checkpoint inhibitors and chimeric antigen receptor-T cells - and can stimulate both innate and adaptive immune responses, even at distant metastatic sites. Here, we review recent progress in this field, with a focus on engineering strategies and their effectiveness in preclinical in vivo tumor models, and outline prospects for future developments and remaining challenges.